AbstractPurposeTo investigate the association between use of methylphenidate and risk of myocardial infarction among Asians.MethodsWe conducted a multinational self‐controlled case series study using nationwide healthcare databases of South Korea (2002–2018), Taiwan (2004–2015), and Hong Kong (2001–2016). Of patients with myocardial infarction who were also prescribed methylphenidate within the observation period, methylphenidate use was classified into four mutually exclusive periods by each person‐day: exposed (exposed to methylphenidate), pre‐exposure (prior to the first methylphenidate prescription), washout (after the end of methylphenidate treatment), and baseline (unexposed to methylphenidate). Risk of myocardial infarction among the three periods of methylphenidate use was compared to the baseline period using conditional Poisson regression analysis to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs).ResultsWe identified 2104, 484, and 30 patients from South Korea, Taiwan, and Hong Kong, respectively. Risk of myocardial infarction was the highest during the pre‐exposure period in all three populations: South Korea, pre‐exposure (IRR 3.17, 95% CI 3.04–3.32), exposed (1.05, 1.00–1.11), washout (1.92, 1.80–2.04); Taiwan, pre‐exposure (1.97, 1.78–2.17), exposed (0.72, 0.65–0.80), washout (0.56, 0.46–0.68); Hong Kong, pre‐exposure (18.09, 8.19–39.96), exposed (9.32, 3.44–25.28), washout (7.69, 1.72–34.41). Following stratification for age and sex, the trends remained analogous to the main findings across all three populations.ConclusionsAlthough a positive association between initiating methylphenidate and the onset of myocardial infarction was observed, the risk was the highest in the period before its initiation. Thus, this multinational study suggests there was no causal relationship between methylphenidate and myocardial infarction among Asians.